OA11603A - Composés tricycliques ayant une activité vis-à-visdes intégrines notamment vis-à-vis de l'intégrine ALPHAvBETA3, leur procédé de préparation et les i ntermédiaires de ce procédé, leur application à titre de médicaments et les compositions pharmaceutiques les renfermant. - Google Patents
Composés tricycliques ayant une activité vis-à-visdes intégrines notamment vis-à-vis de l'intégrine ALPHAvBETA3, leur procédé de préparation et les i ntermédiaires de ce procédé, leur application à titre de médicaments et les compositions pharmaceutiques les renfermant. Download PDFInfo
- Publication number
- OA11603A OA11603A OA9800175A OA9800175A OA11603A OA 11603 A OA11603 A OA 11603A OA 9800175 A OA9800175 A OA 9800175A OA 9800175 A OA9800175 A OA 9800175A OA 11603 A OA11603 A OA 11603A
- Authority
- OA
- OAPI
- Prior art keywords
- formula
- benz
- hexahydro
- hydrazono
- dimethoxy
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims description 118
- 238000002360 preparation method Methods 0.000 title claims description 52
- 238000000034 method Methods 0.000 title claims description 48
- 230000008569 process Effects 0.000 title claims description 14
- 239000003814 drug Substances 0.000 title claims description 10
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 7
- 108010044426 integrins Proteins 0.000 title description 9
- 102000006495 integrins Human genes 0.000 title description 9
- 239000000543 intermediate Substances 0.000 title description 8
- 230000000694 effects Effects 0.000 title description 5
- -1 acyclic hydrocarbon Chemical class 0.000 claims description 165
- 239000000047 product Substances 0.000 claims description 147
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 68
- 239000002253 acid Substances 0.000 claims description 61
- 125000005638 hydrazono group Chemical group 0.000 claims description 55
- 150000002148 esters Chemical class 0.000 claims description 51
- 230000009471 action Effects 0.000 claims description 48
- 125000004432 carbon atom Chemical group C* 0.000 claims description 36
- 239000002585 base Substances 0.000 claims description 33
- 150000003839 salts Chemical class 0.000 claims description 32
- 125000003828 azulenyl group Chemical group 0.000 claims description 27
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 27
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 claims description 27
- 125000003118 aryl group Chemical group 0.000 claims description 25
- 239000003153 chemical reaction reagent Substances 0.000 claims description 24
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 23
- 125000000623 heterocyclic group Chemical group 0.000 claims description 23
- 150000007513 acids Chemical class 0.000 claims description 22
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 21
- 229910052757 nitrogen Inorganic materials 0.000 claims description 21
- 229920006395 saturated elastomer Polymers 0.000 claims description 21
- 239000003795 chemical substances by application Substances 0.000 claims description 17
- UBXPAGGJJMSWLC-UHFFFAOYSA-N 4-hydroxy-2-(phenylmethoxycarbonylamino)butanoic acid Chemical compound OCCC(C(O)=O)NC(=O)OCC1=CC=CC=C1 UBXPAGGJJMSWLC-UHFFFAOYSA-N 0.000 claims description 13
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 12
- 125000005842 heteroatom Chemical group 0.000 claims description 12
- 229910052760 oxygen Inorganic materials 0.000 claims description 12
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 11
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- 229910003827 NRaRb Inorganic materials 0.000 claims description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 8
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- 150000002009 diols Chemical class 0.000 claims description 8
- 229910052701 rubidium Inorganic materials 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 150000001412 amines Chemical group 0.000 claims description 7
- 230000015572 biosynthetic process Effects 0.000 claims description 7
- 125000005843 halogen group Chemical group 0.000 claims description 7
- UKAUYVFTDYCKQA-UHFFFAOYSA-N homoserine Chemical compound OC(=O)C(N)CCO UKAUYVFTDYCKQA-UHFFFAOYSA-N 0.000 claims description 7
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
- 229910052717 sulfur Chemical group 0.000 claims description 7
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
- 125000003282 alkyl amino group Chemical group 0.000 claims description 6
- 150000001413 amino acids Chemical class 0.000 claims description 6
- 230000002140 halogenating effect Effects 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 239000011593 sulfur Chemical group 0.000 claims description 6
- 125000004434 sulfur atom Chemical group 0.000 claims description 6
- LFQGAXHACYZOEZ-UHFFFAOYSA-N 10-hydroxy-8,9-dimethoxy-2,3,5,6-tetrahydro-1h-benzo[e]azulen-4-one Chemical compound C1=2C(O)=C(OC)C(OC)=CC=2CCC(=O)C2=C1CCC2 LFQGAXHACYZOEZ-UHFFFAOYSA-N 0.000 claims description 5
- 239000002168 alkylating agent Substances 0.000 claims description 5
- 229940100198 alkylating agent Drugs 0.000 claims description 5
- 239000003054 catalyst Substances 0.000 claims description 5
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 101100386054 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) CYS3 gene Proteins 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 claims description 4
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 claims description 4
- 101150035983 str1 gene Proteins 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 239000002841 Lewis acid Substances 0.000 claims description 3
- 230000003213 activating effect Effects 0.000 claims description 3
- 125000004450 alkenylene group Chemical group 0.000 claims description 3
- 125000004414 alkyl thio group Chemical group 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims description 3
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- 239000012351 deprotecting agent Substances 0.000 claims description 3
- 150000002430 hydrocarbons Chemical class 0.000 claims description 3
- 150000007517 lewis acids Chemical class 0.000 claims description 3
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims description 3
- 229910052703 rhodium Inorganic materials 0.000 claims description 3
- FVIBVGDZSWMSDR-UHFFFAOYSA-N 4-[[4-(methanehydrazonoylhydrazinylidene)-8,10-dimethoxy-2,3,5,6-tetrahydro-1h-benzo[e]azulen-9-yl]oxy]butanoic acid Chemical compound C1=2C(OC)=C(OCCCC(O)=O)C(OC)=CC=2CCC(=NNC=NN)C2=C1CCC2 FVIBVGDZSWMSDR-UHFFFAOYSA-N 0.000 claims description 2
- TTZXBDFPGHUMAI-UHFFFAOYSA-N CC(CCC(=O)O)OC1=C(C(=C2C(=C1)CCCC3=C2C(=NNC(=O)N)CC3)OC)OC Chemical compound CC(CCC(=O)O)OC1=C(C(=C2C(=C1)CCCC3=C2C(=NNC(=O)N)CC3)OC)OC TTZXBDFPGHUMAI-UHFFFAOYSA-N 0.000 claims description 2
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 2
- KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 claims description 2
- 125000002252 acyl group Chemical group 0.000 claims description 2
- 150000001266 acyl halides Chemical class 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000002947 alkylene group Chemical group 0.000 claims description 2
- 125000000304 alkynyl group Chemical group 0.000 claims description 2
- 125000002619 bicyclic group Chemical group 0.000 claims description 2
- 239000003638 chemical reducing agent Substances 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims description 2
- 239000012374 esterification agent Substances 0.000 claims description 2
- 230000000887 hydrating effect Effects 0.000 claims description 2
- 239000013067 intermediate product Substances 0.000 claims description 2
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims description 2
- 125000002950 monocyclic group Chemical group 0.000 claims description 2
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 2
- 239000003223 protective agent Substances 0.000 claims description 2
- 230000001681 protective effect Effects 0.000 claims description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 2
- TUJKJAMUKRIRHC-UHFFFAOYSA-N hydroxyl Chemical compound [OH] TUJKJAMUKRIRHC-UHFFFAOYSA-N 0.000 claims 3
- MADNYILHDZWZEQ-UHFFFAOYSA-N 4-[[4-(4,5-dihydro-1h-imidazol-2-ylhydrazinylidene)-2,3,5,6-tetrahydro-1h-benzo[e]azulen-8-yl]oxy]butanoic acid Chemical compound C1CC2=CC(OCCCC(=O)O)=CC=C2C(CCC2)=C2C1=NNC1=NCCN1 MADNYILHDZWZEQ-UHFFFAOYSA-N 0.000 claims 1
- RMFOKDWDXRHKNB-UHFFFAOYSA-N 5-[[4-(4,5-dihydro-1h-imidazol-2-ylhydrazinylidene)-9,10-dimethoxy-2,3,5,6-tetrahydro-1h-benzo[e]azulen-8-yl]oxy]pentanoic acid Chemical compound C1CCC2=C1C1=C(OC)C(OC)=C(OCCCCC(O)=O)C=C1CCC2=NNC1=NCCN1 RMFOKDWDXRHKNB-UHFFFAOYSA-N 0.000 claims 1
- LHRRAGKVTFIVHE-UHFFFAOYSA-N 5-[[4-(methanehydrazonoylhydrazinylidene)-8,10-dimethoxy-2,3,5,6-tetrahydro-1h-benzo[e]azulen-9-yl]oxy]pentanoic acid Chemical compound C1=2C(OC)=C(OCCCCC(O)=O)C(OC)=CC=2CCC(=NNC=NN)C2=C1CCC2 LHRRAGKVTFIVHE-UHFFFAOYSA-N 0.000 claims 1
- PJZPXZRMLYZYRN-UHFFFAOYSA-N 5-[[4-(methanehydrazonoylhydrazinylidene)-9,10-dimethoxy-2,3,5,6-tetrahydro-1h-benzo[e]azulen-8-yl]oxy]-3,3-dimethyl-4-oxopentanoic acid Chemical compound C12=C(OC)C(OC)=C(OCC(=O)C(C)(C)CC(O)=O)C=C2CCC(=NNC=NN)C2=C1CCC2 PJZPXZRMLYZYRN-UHFFFAOYSA-N 0.000 claims 1
- SMAVJXLBDMGFEX-UHFFFAOYSA-N 5-[[4-(methanehydrazonoylhydrazinylidene)-9,10-dimethoxy-2,3,5,6-tetrahydro-1h-benzo[e]azulen-8-yl]oxy]pentanoic acid Chemical compound C12=C(OC)C(OC)=C(OCCCCC(O)=O)C=C2CCC(=NNC=NN)C2=C1CCC2 SMAVJXLBDMGFEX-UHFFFAOYSA-N 0.000 claims 1
- XYGPFVUDUMXBLB-UHFFFAOYSA-N 6-[[4-(4,5-dihydro-1h-imidazol-2-ylhydrazinylidene)-9,10-dimethoxy-2,3,5,6-tetrahydro-1h-benzo[e]azulen-8-yl]oxy]hexanoic acid Chemical compound C1CCC2=C1C1=C(OC)C(OC)=C(OCCCCCC(O)=O)C=C1CCC2=NNC1=NCCN1 XYGPFVUDUMXBLB-UHFFFAOYSA-N 0.000 claims 1
- XQIBWECETFJCBP-UHFFFAOYSA-N C1(=CC=C2\C=C\C=CC=C12)N(C(CCO)C(=O)O)C(=O)OCC1=CC=CC=C1 Chemical compound C1(=CC=C2\C=C\C=CC=C12)N(C(CCO)C(=O)O)C(=O)OCC1=CC=CC=C1 XQIBWECETFJCBP-UHFFFAOYSA-N 0.000 claims 1
- 125000004423 acyloxy group Chemical group 0.000 claims 1
- 125000003342 alkenyl group Chemical group 0.000 claims 1
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 claims 1
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid group Chemical group C(CCCCCC)(=O)O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 claims 1
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 1
- 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 164
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- 230000002829 reductive effect Effects 0.000 description 50
- 150000003254 radicals Chemical class 0.000 description 49
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 46
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- 239000002904 solvent Substances 0.000 description 30
- 239000000243 solution Substances 0.000 description 28
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
- 239000000377 silicon dioxide Substances 0.000 description 21
- 239000012043 crude product Substances 0.000 description 20
- 238000004587 chromatography analysis Methods 0.000 description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
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- 229960000510 ammonia Drugs 0.000 description 18
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- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 16
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- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
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- 239000003480 eluent Substances 0.000 description 14
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
- 102000005962 receptors Human genes 0.000 description 14
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- 230000008020 evaporation Effects 0.000 description 12
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 11
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- 208000006386 Bone Resorption Diseases 0.000 description 10
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- 239000012074 organic phase Substances 0.000 description 8
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 8
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- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 6
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- 229960000583 acetic acid Drugs 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- LPIQUOYDBNQMRZ-UHFFFAOYSA-N cyclopentene Chemical compound C1CC=CC1 LPIQUOYDBNQMRZ-UHFFFAOYSA-N 0.000 description 6
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 6
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- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid group Chemical class S(O)(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 238000011282 treatment Methods 0.000 description 6
- QRYZUHYIABOFQJ-UHFFFAOYSA-N 8,9,10-trihydroxy-2,3,5,6-tetrahydro-1h-benzo[e]azulen-4-one Chemical compound C1=2C(O)=C(O)C(O)=CC=2CCC(=O)C2=C1CCC2 QRYZUHYIABOFQJ-UHFFFAOYSA-N 0.000 description 5
- IYMAXBFPHPZYIK-BQBZGAKWSA-N Arg-Gly-Asp Chemical compound NC(N)=NCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O IYMAXBFPHPZYIK-BQBZGAKWSA-N 0.000 description 5
- 150000001408 amides Chemical class 0.000 description 5
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- HAMNKKUPIHEESI-UHFFFAOYSA-N aminoguanidine Chemical group NNC(N)=N HAMNKKUPIHEESI-UHFFFAOYSA-N 0.000 description 5
- 125000004494 ethyl ester group Chemical class 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
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- 235000017557 sodium bicarbonate Nutrition 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
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- 238000012360 testing method Methods 0.000 description 5
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 5
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- 125000004627 thianthrenyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3SC12)* 0.000 description 1
- 125000002769 thiazolinyl group Chemical group 0.000 description 1
- IWVMCIAPBOORJL-UHFFFAOYSA-N thieno[2,3-b]furan Chemical compound C1=CSC2=C1C=CO2 IWVMCIAPBOORJL-UHFFFAOYSA-N 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- 108091007466 transmembrane glycoproteins Proteins 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- CIWZUQUKZAMSIZ-UHFFFAOYSA-N trimethoxy borate Chemical compound COOB(OOC)OOC CIWZUQUKZAMSIZ-UHFFFAOYSA-N 0.000 description 1
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N urethane group Chemical group NC(=O)OCC JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 125000004933 β-carbolinyl group Chemical group C1(=NC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/06—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D239/08—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms directly attached in position 2
- C07D239/12—Nitrogen atoms not forming part of a nitro radical
- C07D239/18—Nitrogen atoms not forming part of a nitro radical with hetero atoms attached to said nitrogen atoms, except nitro radicals, e.g. hydrazine radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C281/00—Derivatives of carbonic acid containing functional groups covered by groups C07C269/00 - C07C279/00 in which at least one nitrogen atom of these functional groups is further bound to another nitrogen atom not being part of a nitro or nitroso group
- C07C281/06—Compounds containing any of the groups, e.g. semicarbazides
- C07C281/08—Compounds containing any of the groups, e.g. semicarbazides the other nitrogen atom being further doubly-bound to a carbon atom, e.g. semicarbazones
- C07C281/12—Compounds containing any of the groups, e.g. semicarbazides the other nitrogen atom being further doubly-bound to a carbon atom, e.g. semicarbazones the carbon atom being part of a ring other than a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C281/00—Derivatives of carbonic acid containing functional groups covered by groups C07C269/00 - C07C279/00 in which at least one nitrogen atom of these functional groups is further bound to another nitrogen atom not being part of a nitro or nitroso group
- C07C281/16—Compounds containing any of the groups, e.g. aminoguanidine
- C07C281/18—Compounds containing any of the groups, e.g. aminoguanidine the other nitrogen atom being further doubly-bound to a carbon atom, e.g. guanylhydrazones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C331/00—Derivatives of thiocyanic acid or of isothiocyanic acid
- C07C331/02—Thiocyanates
- C07C331/04—Thiocyanates having sulfur atoms of thiocyanate groups bound to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C331/00—Derivatives of thiocyanic acid or of isothiocyanic acid
- C07C331/02—Thiocyanates
- C07C331/10—Thiocyanates having sulfur atoms of thiocyanate groups bound to carbon atoms of hydrocarbon radicals substituted by singly-bound oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C331/00—Derivatives of thiocyanic acid or of isothiocyanic acid
- C07C331/02—Thiocyanates
- C07C331/12—Thiocyanates having sulfur atoms of thiocyanate groups bound to carbon atoms of hydrocarbon radicals substituted by nitrogen atoms, not being part of nitro or nitroso groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C331/00—Derivatives of thiocyanic acid or of isothiocyanic acid
- C07C331/02—Thiocyanates
- C07C331/14—Thiocyanates having sulfur atoms of thiocyanate groups bound to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C337/00—Derivatives of thiocarbonic acids containing functional groups covered by groups C07C333/00 or C07C335/00 in which at least one nitrogen atom of these functional groups is further bound to another nitrogen atom not being part of a nitro or nitroso group
- C07C337/06—Compounds containing any of the groups, e.g. thiosemicarbazides
- C07C337/08—Compounds containing any of the groups, e.g. thiosemicarbazides the other nitrogen atom being further doubly-bound to a carbon atom, e.g. thiosemicarbazones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/51—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition
- C07C45/516—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition involving transformation of nitrogen-containing compounds to >C = O groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/63—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by introduction of halogen; by substitution of halogen atoms by other halogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
- C07C45/673—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by change of size of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
- C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
- C07C45/70—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction with functional groups containing oxygen only in singly bound form
- C07C45/71—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction with functional groups containing oxygen only in singly bound form being hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
- C07C49/703—Unsaturated compounds containing a keto groups being part of a ring containing hydroxy groups
- C07C49/747—Unsaturated compounds containing a keto groups being part of a ring containing hydroxy groups containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
- C07C49/753—Unsaturated compounds containing a keto groups being part of a ring containing ether groups, groups, groups, or groups
- C07C49/755—Unsaturated compounds containing a keto groups being part of a ring containing ether groups, groups, groups, or groups a keto group being part of a condensed ring system with two or three rings, at least one ring being a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D233/28—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/44—Nitrogen atoms not forming part of a nitro radical
- C07D233/52—Nitrogen atoms not forming part of a nitro radical with hetero atoms directly attached to said nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/02—Ortho- or ortho- and peri-condensed systems
- C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
- C07C2603/30—Ortho- or ortho- and peri-condensed systems containing three rings containing seven-membered rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9603437A FR2746394B1 (fr) | 1996-03-20 | 1996-03-20 | Nouveaux composes tricycliques, leur procede de preparation, et les intermediaires de ce procede, leur application a titre de medicaments et les compositions pharmaceutiques les renfermant |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| OA11603A true OA11603A (fr) | 2004-08-11 |
Family
ID=9490337
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| OA9800175A OA11603A (fr) | 1996-03-20 | 1998-09-18 | Composés tricycliques ayant une activité vis-à-visdes intégrines notamment vis-à-vis de l'intégrine ALPHAvBETA3, leur procédé de préparation et les i ntermédiaires de ce procédé, leur application à titre de médicaments et les compositions pharmaceutiques les renfermant. |
Country Status (16)
| Country | Link |
|---|---|
| CN (2) | CN1090178C (lt) |
| AR (1) | AR006317A1 (lt) |
| CZ (1) | CZ288898A3 (lt) |
| ES (1) | ES2164337T3 (lt) |
| FR (1) | FR2746394B1 (lt) |
| HR (1) | HRP970163A2 (lt) |
| HU (1) | HUP9902495A3 (lt) |
| IL (1) | IL126106A0 (lt) |
| LT (1) | LT4535B (lt) |
| OA (1) | OA11603A (lt) |
| PL (1) | PL329034A1 (lt) |
| PT (1) | PT888292E (lt) |
| TR (1) | TR199801846T2 (lt) |
| TW (1) | TW458963B (lt) |
| YU (1) | YU40898A (lt) |
| ZA (1) | ZA972393B (lt) |
Family Cites Families (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3044236A1 (de) | 1980-11-25 | 1982-06-16 | Hoechst Ag, 6000 Frankfurt | Aminosaeurederivate und verfahren zu ihrer herstellung |
| DE2937779A1 (de) | 1979-09-19 | 1981-04-09 | Hoechst Ag, 6000 Frankfurt | Aminosaeurederivate und verfahren zu ihrer herstellung |
| FR2487829A2 (fr) | 1979-12-07 | 1982-02-05 | Science Union & Cie | Nouveaux imino acides substitues, leurs procedes de preparation et leur emploi comme inhibiteur d'enzyme |
| FR2503155A2 (fr) | 1980-10-02 | 1982-10-08 | Science Union & Cie | Nouveaux imino diacides substitues, leurs procedes de preparation et leur emploi comme inhibiteur d'enzyme |
| US4350704A (en) | 1980-10-06 | 1982-09-21 | Warner-Lambert Company | Substituted acyl derivatives of octahydro-1H-indole-2-carboxylic acids |
| DE3177130D1 (de) | 1980-08-30 | 1990-01-11 | Hoechst Ag | Aminosaeurederivate, verfahren zu ihrer herstellung, diese enthaltende mittel und deren verwendung. |
| US4344949A (en) | 1980-10-03 | 1982-08-17 | Warner-Lambert Company | Substituted acyl derivatives of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acids |
| FR2492381A1 (fr) | 1980-10-21 | 1982-04-23 | Science Union & Cie | Nouveaux acides aza bicyclo alcane carboxyliques substitues leurs procedes de preparation et leur emploi comme inhibiteur d'enzyme |
| LU88621I2 (fr) | 1980-10-23 | 1995-09-01 | Schering Corp | Sandopril |
| US4374847A (en) | 1980-10-27 | 1983-02-22 | Ciba-Geigy Corporation | 1-Carboxyalkanoylindoline-2-carboxylic acids |
| DE3226768A1 (de) | 1981-11-05 | 1983-05-26 | Hoechst Ag, 6230 Frankfurt | Derivate der cis, endo-2-azabicyclo-(3.3.0)-octan-3-carbonsaeure, verfahren zu ihrer herstellung, diese enthaltende mittel und deren verwendung |
| IE55867B1 (en) | 1981-12-29 | 1991-02-14 | Hoechst Ag | New derivatives of bicyclic aminoacids,processes for their preparation,agents containing these compounds and their use,and new bicyclic aminoacids as intermediates and processes for their preparation |
| DE3210496A1 (de) | 1982-03-23 | 1983-10-06 | Hoechst Ag | Neue derivate bicyclischer aminsaeuren, verfahren zu ihrer herstellung, diese enthaltende mittel und deren verwendung sowie neue bicyclische aminosaeuren als zwischenstufen und verfahren zu deren herstellung |
| DE3211397A1 (de) | 1982-03-27 | 1983-11-10 | Hoechst Ag, 6230 Frankfurt | Spiro (4.(3+n))-2-aza-3-carbonsaeure-derivate, verfahren zu ihrer herstellung, diese enthaltende mittel und ihre verwendung |
| DE3211676A1 (de) | 1982-03-30 | 1983-10-06 | Hoechst Ag | Neue derivate von cycloalka (c) pyrrol-carbonsaeuren, verfahren zu ihrer herstellung, diese enthaltende mittel und deren verwendung sowie neue cycloalka (c) pyrrol-carbonsaeuren als zwischenstufen und verfahren zu deren herstellung |
| DE3227055A1 (de) | 1982-07-20 | 1984-01-26 | Hoechst Ag, 6230 Frankfurt | Neue derivate der 2-aza-bicyclo(2.2.2)octan-3-carbonsaeure, verfahren zu ihrer herstellung, diese enthaltende mittel und deren verwendung sowie 2-aza-bicyclo(2.2.2)octan-3-carbonsaeure als zwischenstufe und verfahren zu deren herstellung |
| DE3242151A1 (de) | 1982-11-13 | 1984-05-17 | Hoechst Ag, 6230 Frankfurt | Neue derivate tricyclischer aminosaeuren, verfahren zu ihrer herstellung, diese enthaltende mittel und deren verwendung, sowie neue bicyclische aminosaeuren als zwischenstufen und verfahren zu deren herstellung |
| DE3246503A1 (de) | 1982-12-16 | 1984-06-20 | Hoechst Ag, 6230 Frankfurt | Derivate der cis, endo-2-azabicyclo-(5.3.0)-decan-3-carbonsaeure, verfahren zu ihrer herstellung, diese enthaltende mittel und deren verwendung |
| DE3643012A1 (de) | 1986-12-17 | 1988-06-30 | Hoechst Ag | 2,3-disubstituierte isoxazolidine, verfahren zu ihrer herstellung, diese enthaltende mittel und ihre verwendung |
| DE3818850A1 (de) | 1988-06-03 | 1989-12-07 | Hoechst Ag | Oligopeptide mit zyklischen prolin-analogen aminosaeuren |
| JPH10504825A (ja) * | 1994-08-22 | 1998-05-12 | スミスクライン・ビーチャム・コーポレイション | 二環式化合物 |
| FR2731217B1 (fr) | 1995-03-03 | 1997-06-13 | Roussel Uclaf | Nouveaux derives tricycliques, leur preparation, leur application a la preparation de la colchicine et de la thiocolchicine optiquement actives ou racemiques et d'analogues ou derives et intermediaires |
-
1996
- 1996-03-20 FR FR9603437A patent/FR2746394B1/fr not_active Expired - Lifetime
-
1997
- 1997-03-19 AR ARP970101095A patent/AR006317A1/es unknown
- 1997-03-19 ZA ZA9702393A patent/ZA972393B/xx unknown
- 1997-03-19 HR HR9603437A patent/HRP970163A2/hr not_active Application Discontinuation
- 1997-03-20 PL PL97329034A patent/PL329034A1/xx unknown
- 1997-03-20 CZ CZ982888A patent/CZ288898A3/cs unknown
- 1997-03-20 CN CN97194806A patent/CN1090178C/zh not_active Expired - Fee Related
- 1997-03-20 IL IL12610697A patent/IL126106A0/xx unknown
- 1997-03-20 ES ES97915519T patent/ES2164337T3/es not_active Expired - Lifetime
- 1997-03-20 PT PT97915519T patent/PT888292E/pt unknown
- 1997-03-20 TR TR1998/01846T patent/TR199801846T2/xx unknown
- 1997-03-20 HU HU9902495A patent/HUP9902495A3/hu unknown
- 1997-09-23 TW TW086113848A patent/TW458963B/zh not_active IP Right Cessation
-
1998
- 1998-09-18 YU YU40898A patent/YU40898A/sh unknown
- 1998-09-18 OA OA9800175A patent/OA11603A/fr unknown
- 1998-10-15 LT LT98-145A patent/LT4535B/lt not_active IP Right Cessation
-
2002
- 2002-06-27 CN CN02141265A patent/CN1401621A/zh active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| PT888292E (pt) | 2002-04-29 |
| HUP9902495A3 (en) | 2001-07-30 |
| IL126106A0 (en) | 1999-05-09 |
| HUP9902495A2 (hu) | 1999-11-29 |
| LT4535B (lt) | 1999-08-25 |
| AR006317A1 (es) | 1999-08-25 |
| YU40898A (sh) | 1999-09-27 |
| HRP970163A2 (en) | 1998-08-31 |
| TW458963B (en) | 2001-10-11 |
| CN1090178C (zh) | 2002-09-04 |
| ZA972393B (en) | 1998-03-19 |
| CN1219165A (zh) | 1999-06-09 |
| CN1401621A (zh) | 2003-03-12 |
| FR2746394B1 (fr) | 1998-05-29 |
| CZ288898A3 (cs) | 1999-03-17 |
| ES2164337T3 (es) | 2002-02-16 |
| LT98145A (lt) | 1999-03-25 |
| TR199801846T2 (xx) | 1998-12-21 |
| PL329034A1 (en) | 1999-03-01 |
| FR2746394A1 (fr) | 1997-09-26 |
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